Modular Hub Genes in DNA Microarray Suggest Potential Signaling Pathway Interconnectivity in Various Glioma Grades

Biology, Journal Year: 2024, Volume and Issue: 13(4), P. 206 - 206

Published: March 23, 2024

Gliomas have displayed significant challenges in oncology due to their high degree of invasiveness, recurrence, and resistance treatment strategies. In this work, the key hub genes mainly associated with different grades glioma, which were represented by pilocytic astrocytoma (PA), oligodendroglioma (OG), anaplastic (AA), glioblastoma multiforme (GBM), identified through weighted gene co-expression network analysis (WGCNA) microarray datasets retrieved from Gene Expression Omnibus (GEO) database. Through this, four highly correlated modules observed be present across PA (GSE50161), OG (GSE4290), AA (GSE43378), GBM (GSE36245) datasets. The functional annotation pathway enrichment done Database for Annotation, Visualization, Integrated Discovery (DAVID) showed that involved signal transduction, transcription regulation, protein binding, collectively deregulate several signaling pathways, PI3K/Akt metabolic pathways. involvement primarily linked other including cAMP, MAPK/ERK, Wnt/β-catenin, calcium indicates potential interconnectivity influence on and, subsequently, glioma severity. Drug Repurposing Encyclopedia (DRE) was used screen drugs based up- downregulated genes, wherein synthetic progestin hormones norgestimate ethisterone top drug candidates. This shows neuroprotective effect progesterone against its EGFR expression Aside these, experimental approved candidates also identified, include an adrenergic receptor antagonist, a PPAR-γ agonist, CDK inhibitor, sodium channel blocker, bradykinin dopamine further highlights as therapeutic avenue glioma.

Language: Английский

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Theoretical Studies of DNA Microarray Present Potential Molecular and Cellular Interconnectivity of Signaling Pathways in Immune System Dysregulation

Genes, Journal Year: 2024, Volume and Issue: 15(4), P. 393 - 393

Published: March 22, 2024

Autoimmunity is defined as the inability to regulate immunological activities in body, especially response external triggers, leading attack of tissues and organs host. Outcomes include onset autoimmune diseases whose effects are primarily due dysregulated immune responses. In past years, there have been cases that show an increased susceptibility other disorders patients who already experiencing same type disease. Research this field has started analyzing potential molecular cellular causes interconnectedness, bearing mind possibility advancing drugs therapies for treatment autoimmunity. With that, study aimed determine correlation four diseases, which 1 diabetes (T1D), psoriasis (PSR), systemic sclerosis (SSc), lupus erythematosus (SLE), by identifying highly preserved co-expressed genes among datasets using WGCNA. Functional annotation was then employed characterize these sets based on their relationship a whole elucidate biological processes, components, functions pathways they involved in. Lastly, drug repurposing analysis performed screen candidate repositioning could abnormal expression diseases. A total thirteen modules were obtained from analysis, majority associated with transcriptional, post-transcriptional, post-translational modification processes. Also, evaluation KEGG suggested possible role TH17 differentiation simultaneous Furthermore, clomiphene top regulating overexpressed hub genes; meanwhile, prilocaine under-expressed genes. This geared towards utilizing transcriptomics approaches assessment microarray data, different use traditional genomic analyses. Such research design investigating correlations may be first its kind.

Language: Английский

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Transcriptomic Analysis of Hub Genes Reveals Associated Inflammatory Pathways in Estrogen-Dependent Gynecological Diseases

Biology, Journal Year: 2024, Volume and Issue: 13(6), P. 397 - 397

Published: May 30, 2024

Gynecological diseases are triggered by aberrant molecular pathways that alter gene expression, hormonal balance, and cellular signaling pathways, which may lead to long-term physiological consequences. This study was able identify highly preserved modules key hub genes mainly associated with gynecological diseases, represented endometriosis (EM), ovarian cancer (OC), cervical (CC), endometrial (EC), through the weighted co-expression network analysis (WGCNA) of microarray datasets sourced from Gene Expression Omnibus (GEO) database. Five were observed across EM (GSE51981), OC (GSE63885), CC (GSE63514), EC (GSE17025) datasets. The functional annotation pathway enrichment revealed heavily involved in several inflammatory transcription dysregulation, such as NF-kB signaling, JAK-STAT MAPK-ERK mTOR pathways. Furthermore, results also include relevant disease prognosis viral infections. Mutations ESR1 encodes for ERα, shown affect inflammation, further indicate its importance prognosis. Potential drugs screened Drug Repurposing Encyclopedia (DRE) based on up-and downregulated genes, wherein a bacterial ribosomal subunit inhibitor benzodiazepine receptor agonist top candidates. Other drug candidates dihydrofolate reductase inhibitor, glucocorticoid agonists, cholinergic selective serotonin reuptake inhibitors, sterol demethylase antifolate, antagonist have known anti-inflammatory effects, demonstrating highlights specific therapeutic avenue designing diseases.

Language: Английский

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Analysis of Modular Hub Genes and Therapeutic Targets across Stages of Non-Small Cell Lung Cancer Transcriptome

Genes, Journal Year: 2024, Volume and Issue: 15(10), P. 1248 - 1248

Published: Sept. 25, 2024

Non-small cell lung cancer (NSCLC), representing 85% of cases, is characterized by its heterogeneity and progression through distinct stages. This study applied Weighted Gene Co-expression Network Analysis (WGCNA) to explore the molecular mechanisms NSCLC identify potential therapeutic targets. expression data from GEO database were analyzed across four stages (NSCLC1, NSCLC2, NSCLC3, NSCLC4), with NSCLC2 dataset selected as reference for module preservation analysis. WGCNA identified eight highly preserved modules—Cyan, Yellow, Red, Dark Turquoise, White, Purple, Royal Blue—across datasets, which enriched in key pathways such “Cell cycle” “Pathways cancer”, involving processes like division inflammatory responses. Hub genes, including PLK1, CDK1, EGFR, emerged critical regulators tumor proliferation immune Estrogen receptor ESR1 was also highlighted, correlating improved survival outcomes, suggesting a prognostic marker. Signature-based drug repurposing analysis promising candidates, GW-5074, inhibits RAF disrupts EGFR–RAS–RAF–MEK–ERK signaling cascade, olomoucine, CDK1 inhibitor. Additional candidates pinocembrin, reduces invasion modulating epithelial-mesenchymal transition, citalopram, an SSRI anti-carcinogenic properties, identified. These findings provide valuable insights into underpinnings suggest new directions strategies repurposing.

Language: Английский

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Signaling Pathways in Clear Cell Renal Cell Carcinoma and Candidate Drugs Unveiled through Transcriptomic Network Analysis of Hub Genes

Applied Sciences, Journal Year: 2024, Volume and Issue: 14(19), P. 8768 - 8768

Published: Sept. 28, 2024

Clear cell renal carcinoma (ccRCC) is a type of kidney cancer. It advances quickly and often metastasizes, making the prognosis for patients challenging. This study used weighted gene co-expression network analysis (WGCNA) to expression data different stages ccRCC obtained in GEO database. The identified three significant highly preserved modules across datasets: GSE53757, GSE22541, GSE66272, GSE73731. Functional annotation pathway enrichment using DAVID revealed inflammatory pathways (e.g., NF-kB, Hippo, HIF-1 pathways) that may drive development progression. also introduced involvement viral infections associated with disease metabolic reprogramming ccRCC. A drug repurposing was conducted identify potential candidates upregulated downregulated hub genes. top are ziprasidone (dopamine serotonin receptor antagonist) fentiazac (cyclooxygenase inhibitor). Other were obtained, such as phosphodiesterase/DNA methyltransferase/ATM kinase inhibitors, acetylcholine antagonists, NAD precursors. Overall, study’s findings suggest identifying several genes signaling related uncover new targets, biomarkers, even drugs can be repurposed, which help develop effective treatments disease.

Language: Английский

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